A major objective of this study is to determine whether the appearance of alpha fetoprotein in the serum of hepatoma-bearing rats is due to (a) de novo synthesis and secretion from healthy hepatoma cells, (b) synthesis without secretion followed by passive release of preformed globulin by injured or dead hepatoma cells. Evidence that primary rat hepatoma cells release preformed alpha fetoprotein into the serum as a result of cell damage and tissue necrosis, rather than by secretion from healthy tumor cells, would explain why detection of serum alpha fetoprotein in rats and man is often limited to the late stages of the disease.